Translational Medical Research Commons^™

Renal Mass Ablation In The Octogenarian And Nonagenarian Population, Callum Hamilton, Amanda Smolock, Md, Colette Shaw, Md, Conor Mckee, Md

Phase 1

Introduction: The gold standard for the management of T1a and T1b renal tumors is partial nephrectomy. This study aims to analyze the outcomes of renal mass thermal ablations as an alternative therapy in the octogenarian and nonagenarian patient population, specifically.

Methods: Departmental database of all percutaneous renal ablations performed between February 2008 and August 2019 was reviewed. 34 tumors were ablated in 19 males and 15 females with a mean age of 84.1 ± 3.1 years (range 80-92 years). Patient demographics, procedural and postprocedural data were evaluated.

Results: Ten microwave and 24 cryoablations were performed, all ablations …

Primary Care Obstructive Sleep Apnea Screening (Pcosa), Alyssa Givens, Risa Goldberg, Cynthia Cheng, Md, Phd

Phase 1

Introduction: Obstructive sleep apnea (OSA) is a largely underdiagnosed disorder of upper airway collapse during sleep. Primary care providers do not routinely screen for OSA. This project aims to determine the yield of using the STOP-BANG questionnaire to identify previously undiagnosed OSA in a primary care population.

Methods: This prospective quality improvement pilot project included 181 patients of the Jefferson Department of Family Medicine identified as high-risk for OSA based on 3 EMR-based search criteria taken from STOP-BANG: hypertension, age >50 years, and BMI >35 kg/m². We attempted contact with patients by mail, followed by up to …

Predictors Of Functional Outcomes Following Operative Treatment Of Acute Achilles Tendon Ruptures, Andrew Fisher, Ryan Rogero, Joseph O'Neil, Md, Daniel Fuchs, Md, Steven Raikin, Md

Phase 1

Introduction: Previous studies involving operative management of Achilles tendon ruptures have attempted to determine if patient factors influence outcomes. No previous study has attempted to identify outcome predictors in patients exclusively undergoing surgical repair. The purpose of this study is to determine if any injury or patient variables were predictive of outcomes following operative management of Achilles ruptures.

Methods: Patient demographics including age, sex, body mass index (BMI), comorbidities (diabetes mellitus, depression, anxiety), mechanism of injury (sports, non-sports), and date of injury were collected. Postoperative notes were reviewed to determine compliance. Patients completed the Foot & Ankle Ability Measure (FAAM)-Activities …

Impact Of Smartphone Usage On Children’S Horizontal Fusional Amplitudes, Jordan Hamburger, Judith Lavrich, Md, Kammi Gunton, Md

Phase 1

Introduction: Cell phone usage has increased in pediatric patients and little research has been done on its effects on patients’ fusional vergence amplitudes. We aim to study the impact of smartphone usage on healthy pediatric patients’ fusional vergence amplitudes and report findings that may lead to future eye problems.

Methods: This is a prospective randomized study. We are currently recruiting healthy patients between the ages of 8-17 years old with no ocular problems. Data collected include refractive error, ocular alignment in the distance and at near, divergence amplitudes at near and in distance, convergence amplitudes at near and in distance, …

Determining The Role Of Surgery In Diagnosis And Treatment Of Primary Cns Lymphoma, Tyler Fox, Michael Baldassari, Lohit Velagapudi, Karim Hafazalla, Christopher J. Farrell, Md, James J. Evans, Md, David W. Andrews, Md, Kevin Judy, Md, Donald Ye, Md

Phase 1

Introduction: Primary central nervous system lymphoma (PCNSL) is a rare entity typically treated with a combination of chemotherapy and radiation. The role of surgery is controversial, and biopsy may be non-definitive or injurious. We review our series of stereotactic and excisional biopsy as well as surgical debulking of PCNSL to quantify overall risk and benefits.

Methods: Patients with biopsy-confirmed intracranial PCNSL were identified from a large singlecenter academic institution between 2012-2018. Preoperative factors and perioperative outcomes were retrospectively reviewed.

Results: A total of 61 cases of PCNSL were identified. Most patients presented with confusion (23.0%), weakness/paralysis (19.7%), and gait disturbance …

Outcomes In Knot Vs Knotless Surgery In Labrum Tears, Zachary Howell, Benjamin Hendy, Md

Phase 1

A Bankart lesion is a tear of the anterior and inferior glenoid labrum. The primary method of repairing this lesion is to sew the detached part back to the joint, however there is a relatively newer method of doing so that does not involve tying a knot in the joint which may cause less joint irritation. The question our research project attempted to answer was: How do the long-term outcomes associated with knotless Bankart labrum repairs compare with the knot repairs? A retrospective cohort study was done with Rothman Institute Bankart lesion patients from 2010-2016. Data was gathered over phone …

Clincial Translational Science Research Of The Functional Role Of Large Conductance Potassium Channels In Selective Destruction Of Triple Negative Breast Cancer Cells, Gina Sizemore

Graduate Theses, Dissertations, and Problem Reports (ETD)

ABSTRACT

The preliminary background that puts this research into context is threefold; it is the aggressive nature of triple negative breast cancer (TNBC), the complexity surrounding its pathology, and the significant lack of targeted treatment for this disease. To clarify the focus of my research, I have concentrated on identifying a targeted treatment for TNBC. In the process, I have identified cycles of reciprocity between treatment, clinical diagnosis, staging, and pathology that will be addressed in smaller papers. However, the weight of this work is in the discovery of a novel target for triple negative breast cancer. The value of …

Obesity And Obstructive Airways Disease: Clinical Correlates And Therapeutic Considerations, John Magagna, Cali Loblundo, Raymond B. Penn, Deepak A. Deshpande, Ajay P. Nayak

Student Papers, Posters & Projects

Obese patients are more likely to suffer from severe asthma symptoms and less likely to be able to control them. In obese patients, there is evidence that shows decreased efficacy of inhaled corticosteroids and beta-2 adrenergic agonists, the core treatment options for achieving and maintaining asthma control. This may be due to mechanical reasons like decreased ventilation and medication delivery, but there are many more pathologies of obesity that interact with pathways of both asthma pathology and asthma control. This review explores the epidemiological significance of obesity, many physiological changes in patients with obesity, the physiological interactions of asthma and …

Conditions For Combining Gene Therapy With Bone Marrow Transplantation In Murine Krabbe Disease., Mohammad Rafi, Paola Luzi, David A Wenger

Department of Neurology Faculty Papers

No abstract provided.

From Bedside To Bench: Use Of Patient-Derived Xenograft Models To Develop Novel Therapeutic Strategies For Triple-Negative Breast Cancer, Tia H. Turner

Theses and Dissertations

Triple-negative breast cancer (TNBC) is a clinically aggressive disease that is associated with bleak outcomes due to its metastatic propensity, frequent failure to respond to chemotherapy, and lack of alternative treatment options. Despite decades of major translational research efforts, there has been very little success thus far in the development of effective targeted therapies for this disease. It is imperative to develop novel therapeutic strategies to improve patient outcomes, as well as minimize the toxicity associated with standard-of-care chemotherapeutics. Given that metastatic disease accounts for the vast majority of TNBC-related deaths, a better understanding of therapeutic responses within common sites …

Effects Of (R,S)-Ketamine And (2r,6r)-Hydroxynorketamine: A Preclinical Study, Remington Rice

Theses and Dissertations

In 2017, 7.1% of US adults were diagnosed with depression, and 50% of patients received medication to treat their depression. Depression can cause severe interruptions in an individual's cognitive functioning and behaviors like sleeping, eating, working, and socializing. Unfortunately, approximately 40% of patients do not respond to treatment with monoaminergic medications (e.g. Prozac) and therapeutic effects may be delayed 2-8 weeks. Due to these therapeutic shortcomings, faster acting and more efficacious treatments are needed. Recent preclinical findings indicate potential for glutamatergic drugs like (R,S)-ketamine and (2R,6R) hydroxynorketamine to produce more rapid and longer-acting therapeutic effects. The antidepressant effectiveness of (R,S)-ketamine …

Exploring The Heteromeric Interface Of The 5-Ht2a-Mglu2 Receptor Complex, Mohamed Aarif Abdul Kareem

Theses and Dissertations

Schizophrenia is a serious mental disorder characteristic of several neurotransmitters including dopamine, serotonin, and glutamate being in imbalance. Early therapies focused solely on dopamine antagonism and second-generation antipsychotics focused on the dopamine and serotonin systems and their respective G protein coupled receptor (GPCR) proteins. Although debate for dimerization of certain classes of GPCR exist, the establishment of an mGlu2-5-HT_2A heterocomplex, which is implicated in schizophrenia is of interest. Previous studies have used a mutation-based approach to identify transmembrane domain 4 (TM4) as the domain responsible in mGlu2 for mediating heteromerization before narrowing down the individual amino acids responsible for …

Biomarkers Of Inflammation In Heart Failure Patients With Reduced And Preserved Ejection Fractions: Multi-Ethnic Study Of Atherosclerosis, Michelle Lynne Stone

UNF Graduate Theses and Dissertations

Purpose Examine the relationships between high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), and soluble tumor necrosis factor-α receptor-1 (sTNF-R1) and the cumulative risk of heart failure with reduced (HFrEF) and preserved (HFpEF) ejection fractions in a diverse, population-based sample. Methods Study sample included 6,814 adult (45-84 years of age) men and women who participated in the Multi-Ethnic Study of Atherosclerosis and were free of cardiovascular disease at baseline. Cox regression was used to calculate the hazard ratios (HR) associated with elevated baseline hs-CRP (> 3-10 mg/L), IL-6 (> 75^th percentile) and sTNF-R1 (> 75^th percentile) and risk of overall …

Interpreting Health Events In Big Data Using Qualitative Traditions, Roschelle L. Fritz, Gordana Dermody

Research outputs 2014 to 2021

© The Author(s) 2020. The training of artificial intelligence requires integrating real-world context and mathematical computations. To achieve efficacious smart health artificial intelligence, contextual clinical knowledge serving as ground truth is required. Qualitative methods are well-suited to lend consistent and valid ground truth. In this methods article, we illustrate the use of qualitative descriptive methods for providing ground truth when training an intelligent agent to detect Restless Leg Syndrome. We show how one interdisciplinary, inter-methodological research team used both sensor-based data and the participant’s description of their experience with an episode of Restless Leg Syndrome for training the intelligent agent. …

Reply To Lipworth Et Al., Angela M. Moran, Sanjay Ramakrishnan, Catherine A. Borg, Clare M. Connolly, Simon Couillard, Christine M. Mwasuku, Ian D. Pavord, Timothy S.C. Hinks, Lauri Lehtimӓki

Research outputs 2014 to 2021

We thank Dr. Lipworth and colleagues for their interest in our work published recently in the Journal (1). They rightly point out that the biology of asthma attacks is more complex than blood eosinophils alone and that corticosteroids have a wide range of other potentially relevant antiinflammatory effects. However, local treatment with inhaled corticosteroids (ICS) is usually the mainstay of patients with frequent eosinophilic exacerbations, and therefore in the great majority of patients, the key question is what oral corticosteroids (OCS) add to ICS in an acute attack (2) and whether this effect is seen with benralizumab. We suggest that …

External Barriers For Including Parents Of Preterm Infants In A Randomised Clinical Trial In The Neonatal Intensive Care Unit In Sweden: A Descriptive Study, Evalotte Mörelius, Emma Olsson, Charlotte Sahlén Helmer, Ylva Thernström Blomqvist, Charlotte Angelhoff

Research outputs 2014 to 2021

© Author(s) (or their employer(s)) 2020. Objectives Performing randomised controlled trials (RCTs) in neonatal intensive care is challenging in many ways. While restrictive inclusion criteria or busy study protocols are obvious barriers, external barriers leading to termination of a study are seldom discussed. The aim of this study was to describe barriers for inclusion of families in neonatal intensive care in an RCT aiming to evaluate the effects of continuous skin-to-skin contact on mood and sleep quality in parents of preterm infants, as well as the quality of parent-infant interaction and salivary cortisol concentrations at the time of discharge. Design …

An Intervention With Dance And Yoga For Girls With Functional Abdominal Pain Disorders (Just In Time): Protocol For A Randomized Controlled Trial, Anna Philipson, Stefan Särnblad, Lars Ekstav, Mats Eriksson, Ulrika L. Fagerberg, Margareta Möller, Evalotte Mörelius, Anna Duberg

Research outputs 2014 to 2021

©Anna Philipson, Stefan Särnblad, Lars Ekstav, Mats Eriksson, Ulrika L Fagerberg, Margareta Möller, Evalotte Mörelius, Anna Duberg. Background: Functional abdominal pain disorders (FAPDs) affect many children worldwide, predominantly girls, and cause considerable long-term negative consequences for individuals and society. Evidence-based and cost-effective treatments are therefore strongly needed. Physical activity has shown promising effects in the practical management of FAPDs. Dance and yoga are both popular activities that have been shown to provide significant psychological and pain-related benefits with minimal risk. The activities complement each other, in that dance involves dynamic, rhythmic physical activity, while yoga enhances relaxation and focus. Objective: …

Brainwave Nets: Are Sparse Dynamic Models Susceptible To Brain Manipulation Experimentation?, Diego C. Nascimento, Marco A. Pinto-Orellana, Joao P. Leite, Dylan J. Edwards, Francisco Louzada, Taiza E.G. Santos

Research outputs 2014 to 2021

© Copyright © 2020 Nascimento, Pinto-Orellana, Leite, Edwards, Louzada and Santos. Sparse time series models have shown promise in estimating contemporaneous and ongoing brain connectivity. This paper was motivated by a neuroscience experiment using EEG signals as the outcome of our established interventional protocol, a new method in neurorehabilitation toward developing a treatment for visual verticality disorder in post-stroke patients. To analyze the [complex outcome measure (EEG)] that reflects neural-network functioning and processing in more specific ways regarding traditional analyses, we make a comparison among sparse time series models (classic VAR, GLASSO, TSCGM, and TSCGM-modified with non-linear and iterative optimizations) …

Eftilagimod Alpha, A Soluble Lymphocyte Activation Gene-3 (Lag-3) Protein Plus Pembrolizumab In Patients With Metastatic Melanoma, Victoria Atkinson, Adnan Khattak, Andrew Haydon, Melissa Eastgate, Amitesh Roy, Prashanth Prithviraj, Christian Mueller, Chrystelle Brignone, Frederic Triebel

Research outputs 2014 to 2021

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. BACKGROUND: To evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics of eftilagimod alpha (efti), a soluble lymphocyte activation gene-3 protein, in combination with the programmed cell death-1 (PD-1) antagonist pembrolizumab. METHODS: The study was divided into two parts; parts A and B, where part A was the dose escalation part and part B was an extension part of the study. Patients with metastatic melanoma were treated with efti plus the standard dose of pembrolizumab. Blood samples were assayed to determine …

Contemporary Epidemiology Of Rising Atrial Septal Defect Trends Across Usa 1991–2016: A Combined Ecological Geospatiotemporal And Causal Inferential Study, Albert Stuart Reece, Gary Kenneth Hulse

Research outputs 2014 to 2021

© 2020, The Author(s). Background: Cardiovascular anomalies are the largest group of congenital anomalies and the major cause of death in young children, with various data linking rising atrial septal defect incidence (ASDI) with prenatal cannabis exposure. Objectives / Hypotheses. Is cannabis associated with ASDI in USA? Is this relationship causal? Methods: Geospatiotemporal cohort study, 1991–2016. Census populations of adults, babies, congenital anomalies, income and ethnicity. Drug exposure data on cigarettes, alcohol abuse, past month cannabis use, analgesia abuse and cocaine taken from National Survey of Drug Use and Health (78.9% response rate). Cannabinoid concentrations from Drug Enforcement Agency. Inverse …

A Drive To Driven Model Of Mapping Intraspecific Interaction Networks., Libo Jiang, Jian Xu, Mengmeng Sang, Yan Zhang, Meixia Ye, Hanyuan Zhang, Biyin Wu, Youxiu Zhu, Peng Xu, Ruyu Tai, Zixia Zhao, Yanliang Jiang, Chuanju Dong, Lidan Sun, Christopher H. Griffin, Claudia Gragnoli, Rongling Wu

Division of Endocrinology, Diabetes and Metabolic Diseases Faculty Papers

Community ecology theory suggests that an individual's phenotype is determined by the phenotypes of its coexisting members to the extent at which this process can shape community evolution. Here, we develop a mapping theory to identify interaction quantitative trait loci (QTL) governing inter-individual dependence. We mathematically formulate the decision-making strategy of interacting individuals. We integrate these mathematical descriptors into a statistical procedure, enabling the joint characterization of how QTL drive the strengths of ecological interactions and how the genetic architecture of QTL is driven by ecological networks. In three fish full-sib mapping experiments, we identify a set of genome-wide QTL …

The Role Of Histone Chaperone Fact Complex In Base Excision Repair Pathway And Its Therapeutic Potential In Colon Cancer And Medulloblastoma, Heyu Song

Theses & Dissertations

Base excision repair (BER) pathway is required for the removal of damaged bases caused by alkylation, oxidation and ring-saturation. Human apurinic/apyrimidinic endonuclease 1 (APE1) plays a central role in BER pathway. Although repair of damaged bases by recombinant APE1 has been well investigated in vitro, how APE1 gains access to damaged bases in the context of chromatin is largely unknown. A prominent member of the histone chaperone family, FACT (Facilitates Chromatin Transcription) is thought to reorganize nucleosomes through the destabilization of multiple intra-nucleosome contacts. FACT complex is composed of two polypeptides identified as SPT16 (Suppressor of Ty 16) and SSRP1 …

The Histone Deacetylase Inhibitor Tubacin Mitigates Endothelial Dysfunction By Up-Regulating The Expression Of Endothelial Nitric Oxide Synthase., Jihui Chen, Jian Zhang, Noor F. Shaik, Bing Yi, Xin Wei, Xiao-Feng Yang, Ulhas P. Naik, Ross Summer, Guijun Yan, Xinyun Xu, Jianxin Sun

Center for Translational Medicine Faculty Papers

Endothelial nitric oxide (NO) synthase (eNOS) plays a critical role in the maintenance of blood vessel homeostasis. Recent findings suggest that cytoskeletal dynamics play an essential role in regulating eNOS expression and activation. Here, we sought to test whether modulation of cytoskeletal dynamics through pharmacological regulation of histone deacetylase 6 (HDAC6)-mediated tubulin deacetylation affects eNOS expression and endothelial function in vitro and in vivo.Wefound that tubulin acetylation inducer (tubacin), a compound that appears to selectively inhibit HDAC6 activity, dramatically increased eNOS expression in several different endothelial cell lines, as determined by both immunoblotting and NO production assays. Mechanistically, we found …

An Analysis Of Abdominal Stability Following Hyperthermic Exercise In Euhydrated And Dehydrated Conditions, Carli Ceckanowicz

Honors Scholar Theses

Core stability is essential for maintaining safety and optimizing performance during exercise and sport. The purpose of this study is to analyze how heat and hydration status (euhydrated USG<1.025 or dehydrated USG>1.025) can impair trunk stability in males and females (in both follicular and luteal phases) using the Trunk Stability Test (TST). Participants complete three blocks of 30 minutes of hyperthermic (35±1.299 ^oC and 49.418±5.0329% relative humidity) treadmill exercise. Exercise intensity is equivalent to 15 minutes at either 11W/kg or 7W/kg and the following 15 minutes at either 7W/kg or 4W/kg, respectively, based on individual heat production data. TST data will …

Preparing Healthcare Staff For Cardiac Arrest Codes In The Outpatient Clinical Setting: Code Drill Training Improves Patient Outcomes, Rowan Edwards, Rn

Master's Projects and Capstones

Preparing Healthcare Staff for Cardiac Arrest Codes in the Outpatient Clinical Setting: Code Drill Training Improves Patient Outcomes

The acuity of care provided in outpatient clinical settings across the United States continues to rise. It is estimated that more than 350,000 cardiac arrests occur outside of a hospital each year (AHA, 2019). For the purpose of this clinical nurse leader (CNL)-lead quality improvement project, the relevant focus is directed towards improving the knowledge, physical skills and perceptions of healthcare staff within an urgent care center (UCC) regarding the application of advanced rescue skills. It is important to note that the …

Underreporting Of Patient-Reported Outcomes In Myeloproliferative Neoplasms Clinical Trials, Anthony Messina, Quentin O'Brien

Clinical Research and Leadership Faculty Posters and Presentations

Introduction

Improvements in overall survival (OS) and quality of life (QoL) are clinically relevant outcomes that should guide clinical decision-making. Patients with MPNs can live with their disease for a long period of time, which increases the importance of understanding the impact of treatment in regards to a patients’ Health-Related QoL. Therefore, including PROs in clinical trials has become paramount in facilitating informed treatment decisions made by health care providers and patients. Furthermore, the FDA encourages the implementation of patient-centric measures in clinical trials.

Objective

We aimed to evaluate the frequency at which PRO measures are utilized as study endpoints …

A Recombinant Cholera Toxin B Subunit Variant (Ctb-Kdel) Exhibits Unique Colon Mucosal Healing Effects That Have Therapeutic Implications For Inflammatory Bowel Disease., Joshua Mark Royal

Electronic Theses and Dissertations

This dissertation uncovers the mechanism and explores the utility of a recombinant cholera toxin B subunit (CTB) variant containing a KDEL endoplasmic reticulum (ER) retention motif (CTB-KDEL) as a drug candidate for the treatment of inflammatory bowel disease (IBD). CTB is a mucosal immunomodulatory protein that induces robust mucosal and systemic antibody responses. This well-known biological activity has been exploited in cholera prevention (as a component of Dukoral® vaccine) and vaccine development for decades. On the other hand, several studies have investigated CTB’s immunotherapeutic potential in the treatment of inflammatory diseases such as Crohn’s disease and asthma. Here, we reveal …

Relevance Of Fgfr1 And Its Isoforms In Prostate Cancer Bone Metastases, Estefania Labanca

Dissertations and Theses (Open Access)

The fibroblast growth factor receptor (FGFR) 1 is implicated in prostate cancer (PCa) progression. Various FGFR1 isoforms have been described and we demonstrate here that the well-characterized FGFR1 a and b isoforms are correlated with the expression of different genes and pathways in human PCa. Direct injection of PC3 PCa cells overexpressing FGFR1 isoforms into the femur of mice resulted in enhanced tumor growth and reduction in bone volume when compared with PC3 expressing empty vector. However, only PC3 overexpressing FGFR1 b was associated with increased osteoclast parameters, suggesting that each isoform may mediate diverse biological effects (similar findings were …

Hypothyroidism, Sex And Age Predict Future Thromboembolic Events Among Younger People, Supplementary Table 1, Jay A. Martinez, Fares Qeadan, Mark R. Burge

Clinical and Translational Science Center Scholarly Output

This is Supplementary Table 1 for a forthcoming publication in the Journal of Clinical Endocrinology and Metabolism, entitled "Hypothyroidism, Sex and Age Predict Future Thromboembolic Events Among Younger People," by Authors Jay A. Martinez, Fares Qeadan, PhD, and Mark R. Burge, MD

Supplement Table 1: ICD-9 and ICD-10 codes employed in this study for inclusion and exclusion purposes.

Community-Acquired Pneumonia Pathogenesis In Patients With Chronic Obstructive Pulmonary Disease, Julio A. Ramirez, Rodrigo Cavallazzi

The University of Louisville Journal of Respiratory Infections

No abstract provided.